: The goal of this research is to understand the endoplasmic reticulum (ER) stress signaling pathways and the resultant activation of specific cellular caspases following infection by a cytoplasmic RNA virus. Specifically, the overall objective is to characterize these pathways in programmed cell death (apoptosis), and determine the mechanism of their activation by specific viral gene products. These studies draw on recent research on host-virus interaction, especially the demonstration of caspasedependent apoptosis of lung epithelial cells by respiratory syncytial virus (RSV), by far the most important pathogen of the lower respiratory tract. RSV-infection leads to massive destruction of the lung cells, and an annual death toll of nearly a million people, mostly infants. In cell culture, infection of the lung epithelial cells by RSV leads to the induction of pro-inflammatory cytokines, and the apoptotic death program. Thus, in-depth studies of the role of specific caspases in lung cell apoptosis, activation of the ER stress response, and the relationship between the two are proposed. Together, these results will shed light on strategic areas of host-virus interaction, which will be essential to our understanding of pathogenesis of RSV in particular and RNA viruses in general.